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1.
Cell ; 187(21): 5981-5997.e14, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39243765

RESUMO

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.


Assuntos
Tosse , Espirro , Animais , Camundongos , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/fisiologia , Células Receptoras Sensoriais/virologia , Masculino , Mucosa Nasal/virologia , Mucosa Nasal/metabolismo , Feminino , Traqueia/virologia , Camundongos Endogâmicos C57BL , Humanos , Receptores Acoplados a Proteínas G/metabolismo
2.
Cell ; 184(14): 3762-3773.e10, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34133943

RESUMO

Sneezing is a vital respiratory reflex frequently associated with allergic rhinitis and viral respiratory infections. However, its neural circuit remains largely unknown. A sneeze-evoking region was discovered in both cat and human brainstems, corresponding anatomically to the central recipient zone of nasal sensory neurons. Therefore, we hypothesized that a neuronal population postsynaptic to nasal sensory neurons mediates sneezing in this region. By screening major presynaptic neurotransmitters/neuropeptides released by nasal sensory neurons, we found that neuromedin B (NMB) peptide is essential for signaling sneezing. Ablation of NMB-sensitive postsynaptic neurons in the sneeze-evoking region or deficiency in NMB receptor abolished the sneezing reflex. Remarkably, NMB-sensitive neurons further project to the caudal ventral respiratory group (cVRG). Chemical activation of NMB-sensitive neurons elicits action potentials in cVRG neurons and leads to sneezing behavior. Our study delineates a peptidergic pathway mediating sneezing, providing molecular insights into the sneezing reflex arc.


Assuntos
Tronco Encefálico/fisiopatologia , Neuropeptídeos/metabolismo , Nariz/fisiopatologia , Reflexo/fisiologia , Espirro/fisiologia , Animais , Modelos Animais de Doenças , Hipersensibilidade/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Neurocinina B/análogos & derivados , Neurocinina B/metabolismo , Neurônios/metabolismo , RNA Interferente Pequeno/metabolismo , Células Receptoras Sensoriais/fisiologia , Canais de Cátion TRPV/metabolismo , Gravação em Vídeo
3.
Proc Natl Acad Sci U S A ; 120(2): e2204134120, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36595669

RESUMO

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only mild changes with <15 dysregulated genes. The constitutive cell types that accomplish homeostatic renewal were conserved in DED but were associated with activation of cell states that comprise "adaptive regeneration." We provide global markers that distinguish cell types in homeostatic renewal vs. adaptive regeneration and markers that specifically define DED-elicited proliferating and differentiating cell types. We validate that expression of SPARC, a marker of adaptive regeneration, is also induced in corneal epithelial wound healing and accelerates wound closure in a corneal epithelial cell scratch assay. Finally, we propose a classification system for LSC markers based on their expression fidelity in homeostasis and disease. This transcriptional dissection uncovers the dramatically altered transcriptional landscape of the corneal epithelium in DED, providing a framework and atlas for future study of these ocular surface stem cells in health and disease.


Assuntos
Síndromes do Olho Seco , Epitélio Corneano , Limbo da Córnea , Camundongos , Animais , Limbo da Córnea/fisiologia , Diferenciação Celular/fisiologia , Córnea , Cicatrização/genética , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/metabolismo , Homeostase/genética
4.
Toxicol Appl Pharmacol ; 492: 117125, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39395609

RESUMO

Oral small-molecule GLP-1 receptor biased agonists exhibit promising treatment efficacy of type 2 diabetes and obesity. SAL0112 is a novel compound that has demonstrated remarkable efficacy in preclinical animal models. Herein, both in vitro and in vivo preclinical toxicity investigations were conducted to explore the safety profile of SAL0112. The HTRF assay and TR-FRET assay were utilized for cAMP detection. Patch clamp assay was employed for hERG potassium ion channel determination. Cynomolgus monkeys were used in a cardiovascular safety pharmacology study and a 13-week repeated dose toxicity study. The telemetry system was employed to detect cardiovascular indicators such as ECG, HR, and BP. During the repeated dose toxicity study, body weight, food intake, hematology, coagulation function test, serum biochemistry tests, and urine analysis were measured. Macroscopic and microscopic observations were conducted at the end of the study. TK studies were conducted on Day 1 and Day 91. SAL0112 exhibited a high degree of potency in activating the monkey GLP-1 receptor whereas had no effect on the rodent GLP-1 receptor. In contrast to Danuglipron, which demonstrated high potency on hERG with an IC50 value of 6.9 µM, the IC50 of SAL0112 on hERG was greater than 100 µM. Compared to the Vehicle Control group, no significant changes in cardiovascular indicators were observed in the cardiovascular safety pharmacology study after a single dose of SAL0112 up to 250 mg/kg (P > 0.05). A repeated dose toxicity study revealed moderate anorexigenic effects and a reduction in body weight, effects that were found to be reversible and not associated with any pathological changes. The NOAEL of SAL0112 is 150 mg/kg, providing an approximate safety margin of threefold. SAL0112 demonstrated a favorable safety profile in cynomolgus monkeys, with a substantial therapeutic window that supports the progression of this compound into clinical studies.

5.
Sensors (Basel) ; 22(16)2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-36016050

RESUMO

At present, PPF-based point cloud recognition algorithms can perform better matching than competitors and be verified in the case of severe occlusion and stacking. However, including certain superfluous feature point pairs in the global model description would significantly lower the algorithm's efficiency. As a result, this paper delves into the Point Pair Feature (PPF) algorithm and proposes a 6D pose estimation method based on Keypoint Pair Feature (K-PPF) voting. The K-PPF algorithm is based on the PPF algorithm and proposes an improved algorithm for the sampling point part. The sample points are retrieved using a combination of curvature-adaptive and grid ISS, and the angle-adaptive judgment is performed on the sampling points to extract the keypoints, therefore improving the point pair feature difference and matching accuracy. To verify the effectiveness of the method, we analyze the experimental results in scenes with different occlusion and complexity levels under the evaluation metrics of ADD-S, Recall, Precision, and Overlap rate. The results show that the algorithm in this paper reduces redundant point pairs and improves recognition efficiency and robustness compared with PPF. Compared with FPFH, CSHOT, SHOT and SI algorithms, this paper improves the recall rate by more than 12.5%.


Assuntos
Algoritmos
6.
Lipids Health Dis ; 20(1): 151, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727932

RESUMO

BACKGROUND: Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. METHODS: In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. RESULTS: Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. CONCLUSIONS: The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.


Assuntos
Carnitina/análogos & derivados , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/metabolismo , Metabolismo dos Lipídeos , Adulto , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacologia , Animais , Biomarcadores/sangue , Carnitina/sangue , Carnitina/química , Carnitina/farmacologia , Linhagem Celular , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Mioblastos Cardíacos/efeitos dos fármacos , Mioblastos Cardíacos/metabolismo , Ácidos Mirísticos/farmacologia , Ratos , Estudos Retrospectivos , Ribonucleosídeos/farmacologia , Fatores de Risco
7.
J Headache Pain ; 20(1): 93, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477012

RESUMO

BACKGROUND: Increasing evidence has suggested that the cerebellum is associated with pain and migraine. In addition, the descending pain system of the brainstem is the major site of trigeminal pain processing and modulation and has been discussed as a main player in the pathophysiology of migraine. Cerebellar and brainstem structural changes associated with migraineurs remain to be further investigated. METHODS: Voxel-based morphometry (VBM) (50 controls, 50 migraineurs without aura (MWoAs)) and diffusion tensor imaging (DTI) (46 controls, 46 MWoAs) were used to assess cerebellum and brainstem anatomical alterations associated with MWoAs. We utilized a spatially unbiased infratentorial template toolbox (SUIT) to perform cerebellum and brainstem optimized VBM and DTI analysis. We extracted the average diffusion values from a probabilistic cerebellar white matter atlas to investigate whether MWoAs exhibited microstructure alterations in the cerebellar peduncle tracts. RESULTS: MWoAs showed decreased fractional anisotropy (FA) in the vermis VI extending to the bilateral lobules V and VI of the cerebellum. We also found higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in the right inferior cerebellum peduncle tract in MWoAs. MWoAs exhibited both reduced gray matter volume and increased AD, MD and RD in the spinal trigeminal nucleus (SpV). CONCLUSION: MWoAs exhibited microstructural changes in the cerebellum and the local brainstem. These structural differences might contribute to dysfunction of the transmission and modulation of noxious information, trigeminal nociception, and conduction and integration of multimodal information in MWoAs. These findings further suggest involvement of the cerebellum and the brainstem in the pathology of migraine without aura.


Assuntos
Tronco Encefálico/patologia , Cerebelo/patologia , Enxaqueca sem Aura/patologia , Anisotropia , Tronco Encefálico/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Masculino , Enxaqueca sem Aura/diagnóstico por imagem , Núcleo Espinal do Trigêmeo/diagnóstico por imagem , Núcleo Espinal do Trigêmeo/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
8.
Anal Biochem ; 520: 9-15, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28024754

RESUMO

An electrochemical sensor with high selectivity in addition to sensitivity was developed for the determination of cardiac troponin I (cTnI), based on the modification of cTnI imprinted polymer film on a glassy carbon electrode (GCE). The sensor was fabricated by layer-by-layer assembled graphene nanoplatelets (GS), multiwalled carbon nanotubes (MWCNTs), chitosan (CS), glutaraldehyde (GA) composites, which can increase the electronic transfer rate and the active surface area to capture a larger number of antigenic proteins. MWCNTs/GS based imprinted polymers (MIPs/MWCNTs/GS) were synthesized by means of methacrylic acid (MAA) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the cross linker α,α'-azobisisobutyronitrile (AIBN) as the initiator and cTnI as the template. In comparison with conventional methods, the proposed electrochemical sensor is highly sensitive for cTnI, providing a better linear response range from 0.005 to 60 ng cm-3 and a lower limit of detection (LOD) of 0.0008 ng cm-3 under optimal experimental conditions. In addition, the electrochemical sensor exhibited good specificity, acceptable reproducibility and stability. Moreover, satisfactory results were obtained in real human serum samples, indicating that the developed method has the potential to find application in clinical detection of cTnI as an alternative approach.


Assuntos
Técnicas Eletroquímicas , Grafite/química , Impressão Molecular , Nanoestruturas/química , Nanotubos de Carbono/química , Troponina I/análise , Carbono/química , Eletrodos , Humanos , Limite de Detecção , Microscopia Eletrônica de Varredura , Miocárdio/metabolismo , Polímeros/química , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier
9.
J Stroke Cerebrovasc Dis ; 24(8): e205-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26123876

RESUMO

BACKGROUND: Here we report a rare case of repeated transient Wallenberg's syndrome and discuss its mechanism. METHODS: Case report and literature review. RESULTS: A 57-year-old man was admitted for 1.5-month repeated transient Wallenberg's syndrome, including right-sided Horner's syndrome, lower limb weakness, and paresthesia on the right side of the body and face. His symptom appeared mostly during physical activity. Symptoms occurred nearly everyday and lasted from 5 minutes to 30 minutes. His cranial magnetic resonance imaging (MRI) including diffusion-weighted MRI imaging was normal, and his cervical contrast-enhanced magnetic resonance angiography reflected right vertebral artery hypoplasia. Twenty-four-hour electrocardiogram and electroencephalography showed no abnormalities. Echocardiography showed aortic valve calcification with moderate aortic stenosis, moderate aortic insufficiency, and dilated aorta. Dual-antiplatelets or warfarin (international normalized ratio reached 2.07) were not effective to reduce the attacks. CONCLUSIONS: Hemodynamic instability due to valve disease combined with right vertebral artery hypoplasia could lead to transient Wallenberg's syndrome. Antithrombotics are often ineffective for this kind of patients and the best therapy for them could be to cure their valve disease. Repeated transient Wallenberg's syndrome is rare and that caused by ipsilateral vertebral artery hypoplasia and severe valve disease has not been reported up till now to our knowledge, so it will widen the knowledge on etiologies of transient ischemic attacks and provide information and reference to cardiologists and neurologists in diagnosis and treatment for patients with similar clinical manifestations.


Assuntos
Lateralidade Funcional , Cardiopatias Congênitas/complicações , Doenças das Valvas Cardíacas/complicações , Síndrome Medular Lateral/complicações , Artéria Vertebral/patologia , Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Ecocardiografia , Síndrome de Horner/etiologia , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
10.
J Org Chem ; 79(6): 2473-80, 2014 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-24559389

RESUMO

The catalytic enantioselective and divergent total syntheses of Aspidosperma alkaloids (+)-10-oxocylindrocarpidine 7, (+)-cylindrocarpidine 1, (-)-N-acetylcylindrocarpinol 6, and (+)-aspidospermine 8 have been accomplished in 11 steps from a common precursor (15) on the basis of a highly concise route. The route features three metal-catalyzed reactions, including the key Pd-catalyzed decarboxylative asymmetric allylation of carbazolones developed in our laboratory. Our syntheses, using a combination of C-H activation, enantioselective catalysis, and collective synthesis, represent the first total synthesis of 10-oxocylindrocarpidine and the first asymmetric total synthesis of cylindrocarpidine and N-acetylcylindrocarpinol.


Assuntos
Alcaloides/síntese química , Aspidosperma/química , Alcaloides Indólicos/síntese química , Quinolinas/síntese química , Alcaloides/química , Catálise , Alcaloides Indólicos/química , Estrutura Molecular , Quinolinas/química , Estereoisomerismo
11.
Food Chem ; 456: 139868, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38870825

RESUMO

The freezing point (FP) is an important quality indicator of the superchilled meat. Currently, the potential of hyperspectral imaging (HSI) for predicting beef FP as affected by multiple freeze-thaw (F-T) cycles was explored. Correlation analysis revealed that the FP had a negative correlation with the proportion of bound water (P21) and a positive correlation with the proportion of immobilized water (P22). Moreover, the optimal wavelengths were selected by principal component analysis (PCA). Principal component regression (PCR) and partial least squares regression (PLSR) models were successfully developed based on the optimal wavelengths for predicting FP with determination coefficient in prediction (RP2) of 0.76, 0.76 and root mean square errors in prediction (RMSEP) of 0.12, 0.12, respectively. Additionally, PLSR based on full wavelengths was established for predicting P21 with RP2 of 0.80 and RMSEP of 0.67, and PLSR based on the optimal wavelengths was established for predicting P22 with RP2 of 0.87 and RMSEP of 0.66. The results show the potential of hyperspectral technology to predict the FP and moisture distribution of meat as a nondestructive method.


Assuntos
Congelamento , Imageamento Hiperespectral , Água , Animais , Bovinos , Água/análise , Água/química , Imageamento Hiperespectral/métodos , Análise de Componente Principal , Carne/análise , Análise dos Mínimos Quadrados , Temperatura de Transição , Carne Vermelha/análise
12.
Mater Horiz ; 11(10): 2457-2468, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38465967

RESUMO

In vivo transmembrane-voltage detection reflected the electrophysiological activities of the biological system, which is crucial for the diagnosis of neuronal disease. Traditional implanted electrodes can only monitor limited regions and induce relatively large tissue damage. Despite emerging monitoring methods based on optical imaging have access to signal recording in a larger area, the recording wavelength of less than 1000 nm seriously weakens the detection depth and resolution in vivo. Herein, a Förster resonance energy transfer (FRET)-based nano-indicator, NaYbF4:Er@NaYF4@Cy7.5@DPPC (Cy7.5-ErNP) with emission in the near-infrared IIb biological window (NIR-IIb, 1500-1700 nm) is developed for transmembrane-voltage detection. Cy7.5 dye is found to be voltage-sensitive and is employed as the energy donor for the energy transfer to the lanthanide nanoparticle, NaYbF4:Er@NaYF4 (ErNP), which works as the acceptor to achieve electrophysiological signal responsive NIR-IIb luminescence. Benefiting from the high penetration and low scattering of NIR-IIb luminescence, the Cy7.5-ErNP enables both the visualization of action potential in vitro and monitoring of Mesial Temporal lobe epilepsy (mTLE) disease in vivo. This work presents a concept for leveraging the lanthanide luminescent nanoprobes to visualize electrophysiological activity in vivo, which facilitates the development of an optical nano-indicator for the diagnosis of neurological disorders.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Nanopartículas , Animais , Transferência Ressonante de Energia de Fluorescência/métodos , Imagem Óptica/métodos , Camundongos , Fenômenos Eletrofisiológicos/fisiologia , Raios Infravermelhos , Humanos , Masculino , Ratos , Potenciais de Ação/fisiologia , Corantes Fluorescentes
13.
J Org Chem ; 78(22): 11444-9, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24131444

RESUMO

Evolution of the synthetic strategy that culminated in the first asymmetric total synthesis of the Aspidosperma alkaloid limaspermidine is described. The successful enantioselective route to (-)-limaspermidine proceeds in 10 steps and with the isolation of only six intermediates using a Pd-catalyzed enantioselective decarboxylative allylation we have recently developed. This first enantioselective synthesis of (-)-limaspermidine establishes unambiguously its absolute configuration and allows the first asymmetric formal total synthesis of the Aspidoalbine alkaloid (-)-1-acetylaspidoalbidine.


Assuntos
Alcaloides Indólicos/síntese química , Alcaloides Indólicos/química , Estrutura Molecular , Estereoisomerismo
14.
Analyst ; 138(6): 1828-34, 2013 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-23370308

RESUMO

Cancer antigen 125 (CA 125) is a useful tumor marker with a threshold value of 35 U mL(-1) expressed by more than 80% of patients with non-mucinous epithelial ovarian cancer. In this work, a novel strategy for the analysis of CA 125 using the plasmon resonance scattering (PRS) properties of gold nanorods was proposed. The gold nanorod (GNR)-anti-CA 125 conjugates were prepared first. The immunoreaction between the GNR modified CA 125 antibody and CA 125 took place in aqueous solution after the addition of CA 125. The target protein concentration was determined by analyzing the level of GNR aggregation caused by CA 125 antibody-antigen interactions using PRS. At a concentration of 1.0-80 U mL(-1), CA 125 could be determined with a detection limit of 0.4 U mL(-1). The PRS immunosensor showed high sensitivity, selectivity, and reproducibility. Determination of CA 125 in serum samples showed good recovery.


Assuntos
Antígeno Ca-125/sangue , Ouro/química , Nanotubos/química , Ressonância de Plasmônio de Superfície/métodos , Anticorpos Imobilizados/química , Humanos , Limite de Detecção
15.
J Infect Public Health ; 16(2): 155-162, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36535135

RESUMO

BACKGROUND: Accumulating studies demonstrated that patients with coronavirus disease 2019(COVID-19) could develop a variety of neurological manifestations and long-term neurological sequelae, which may be different from the strains. At the peak of the Omicron variant outbreak in Shanghai, China, no relevant epidemiological data about neurological manifestations associated with this strain was reported. OBJECTIVE: To investigate neurological manifestations and related clinical features in patients with mild to moderate COVID-19 patients with Omicron variant. METHODS: A self-designed clinical information registration form was used to gather the neurological manifestations of mild to moderate COVID-19 patients admitted to a designated hospital in Shanghai from April 18, 2022 to June 1, 2022. Demographics, clinical presentations, laboratory findings, treatments and clinical outcomes were compared between patients with and without neurological manifestations. RESULTS: One hundred sixty-nine(48.1 %) of 351 patients diagnosed with mild to moderate COVID-19 exhibited neurological manifestations, the most common of which were fatigue/weakness(25.1 %) and myalgia(20.7 %), whereas acute cerebrovascular disease(0.9 %), impaired consciousness(0.6 %) and seizure(0.6 %) were rare. Younger age(p = 0.001), female gender(p = 0.026) and without anticoagulant medication(p = 0.042) were associated with increasing proportions of neurological manifestations as revealed by multivariate logistic regressions. Patients with neurological manifestations had lower creatine kinase and myoglobin levels, as well as higher proportion of patchy shadowing on chest scan. Vaccination status, clinical classification of COVID-19 and clinical outcomes were similar between the two groups. CONCLUSIONS: Nearly half of the involved patients have neurological manifestations which were relatively subjective and closely associated with younger age, female gender and without anticoagulation. Patients with neurologic manifestations may be accompanied by increased lung patchy shadowing.


Assuntos
COVID-19 , Humanos , Feminino , China/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , SARS-CoV-2 , Pacientes
16.
Front Aging Neurosci ; 15: 1138418, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213541

RESUMO

Background: Clinical manifestations of Parkinson's disease (PD) after Corona Virus Disease 2019 (COVID-19) infection are poorly investigated. Objective: We aimed to explore the clinical features and outcomes of hospitalized PD patients with COVID-19. Methods: A total of 48 PD patients and 96 age-and sex-matched non-PD patients were included. Demographics, clinical characteristics and outcomes were compared between two groups. Results: PD patients with COVID-19 were elderly (76.69 ± 9.21 years) with advanced stage (H-Y stage 3-5 as 65.3%). They had less clinical symptoms (nasal obstruction, etc.), more proportions of severe/critical COVID-19 clinical classification (22.9 vs. 1.0%, p < 0.001), receiving oxygen (29.2 vs. 11.5%, p = 0.011), antibiotics (39.6 vs. 21.9%, p = 0.031) therapies, as well as longer hospitalization duration (11.39 vs. 8.32, p = 0.001) and higher mortality (8.3% vs. 1.0%, p = 0.001) relative to those without PD. Laboratory results showed that the PD group had higher white blood cell counts (6.29 vs. 5.16*109, p = 0.001), neutrophil-to-lymphocyte ratio (3.14 vs. 2.11, p < 0.001) and C-reactive protein level (12.34 vs. 3.19, p < 0.001). Conclusion: PD patients with COVID-19 have insidious clinical manifestation, elevated proinflammatory markers and are prone to the development of severe/critical condition, contributing to a relatively poor prognosis. Early identification and active treatment of COVID-19 are pivotal to advanced PD patients during the pandemic.

17.
BMC Neurosci ; 13: 154, 2012 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-23272656

RESUMO

BACKGROUND: There are two widely used transient middle cerebral artery occlusion (MCAO) methods, which differ in the use of unilateral or bilateral carotid artery reperfusion (UNICAR and BICAR). Of the two methods, UNICAR is easier to perform. This study was designed to comprehensively compare the two reperfusion methods to determine if there are any differences in outcomes. RESULTS: The UNICAR and BICAR groups each included 9 rats. At baseline, the average pO(2) was 20.54 ± 9.35 and 26.43 ± 7.39, for the UNICAR and BICAR groups, respectively (P = 0.519). Changes in pO(2), as well as other physiological parameters measured within the ischemic lesion, were similar between the UNICAR and BICAR groups during 90 min of MCAO and the first 30 min of reperfusion (all P > 0.05). Furthermore, both the Bederson score and Garcia score, which are used for neurological assessment, were also similar (both P > 0.05). There were also no significant differences in T2WI lesion volume, DWI lesion volume, PWI lesion volume, or TTC staining infarct volume between the two groups (all P > 0.05). CONCLUSION: UNICAR and BICAR have similar capability for inducing acute brain ischemic injury and can be considered interchangeable up to 24 hours after reperfusion.


Assuntos
Circulação Cerebrovascular/fisiologia , Infarto da Artéria Cerebral Média/patologia , Traumatismo por Reperfusão/patologia , Reperfusão/métodos , Animais , Imagem de Difusão por Ressonância Magnética/métodos , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/mortalidade , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Neuroimagem/métodos , Exame Neurológico , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/mortalidade , Traumatismo por Reperfusão/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo
18.
Front Med (Lausanne) ; 9: 1038938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419783

RESUMO

Background: Olfactory dysfunction is a common neurological symptom of Corona Virus Disease 2019(COVID-19). Little is known about hyposmia after COVID-19 infection with Omicron variant in Chinese population. Objective: To investigate the incidence, clinical characteristics and recovery of hyposmia in hospitalized non-severe COVID-19 patients with Omicron variant in Shanghai, China. Methods: Three hundred and forty-nine Chinese non-severe COVID-19 patients with Omicron variant were consecutively enrolled in a designated hospital to investigate the incidence of hyposmia in hospitalization and the recovery rate 1 month later. The visual assessment scale (VAS) was used to evaluate the severity of hyposmia. We compared the demographic, clinical features and treatment outcomes, as well as laboratory parameters between patients with and without hyposmia. Results: The cross-sectional survey showed that 22 (6.3%) hospitalized patients with non-severe COVID-19 had hyposmia. Patients with hyposmia were younger (61.5 vs. 72.0, p = 0.002), had more related clinical symptoms (sore throat, cough, poor appetite, diarrhea, myalgia and taste impairment, etc.), a higher proportion of moderate clinical type (31.8 vs. 13.5%, p = 0.028) and longer duration of hospitalization (11 vs. 8 days, p = 0.027) than those without hyposmia. Whereas, there were no significant differences regarding gender, comorbidity and nucleic acid conversion time between the two groups. Laboratory subgroup analyses demonstrated that patients with hyposmia had slightly low serum IL-6 and TNF-α levels. However, both of the levels were not associated with hyposmia occurrence in multivariate regression analyses. Further follow-up study disclosed that 16 of 22 (72.7%) hyposmia patients had recovered olfaction 1 month later. Serum IL-6 and TNF-α levels were similar between hyposmia recovered patients and those with persistent hyposmia. Conclusion: Although the incidence of hyposmia after Omicron variant infection is relatively low and the short-term recovery rate is quite high, patients with hyposmia are prone to have a higher proportion of both upper and lower respiratory tract involvements, gastrointestinal and neurological symptoms, contributing to a longer duration of hospitalization.

19.
Front Public Health ; 10: 1006610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420001

RESUMO

Objectives: Medical workers are prone to psychological and sleep disturbances during the coronavirus disease 2019 (COVID-19) pandemic. Little is known about the varying degrees of influence among vaccinated medical staff working in different positions. The current study is aimed to evaluate and compare depression, anxiety and sleep disturbances among first-line, second-line and at home vaccinated medical staff during the COVID-19 pandemic in Shanghai, China. Methods: A cross-sectional online survey was conducted in May 2022. In addition to demographic data, levels of depression, anxiety, sleep quality, and insomnia were measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Pittsburgh Sleep Quality Index (PSQI), and Athens Insomnia Scale (AIS). Results: A total of 236 vaccinated medical workers completed the questionnaires, including 85 first-line medical staff (FMS), 82 second-line medical staff (SMS) and 69 at home medical staff (HMS). The proportions of depressive symptoms, anxiety symptoms, poor sleep quality, and insomnia were 52.1, 44.1, 55.9, and 49.2%, respectively. Compared with HMS, medical staff at work (FMS and SMS) got significantly higher frequency of poor sleep quality (both p < 0.001), insomnia (both p < 0.001), depressive (p < 0.001 and p = 0.003, respectively) and anxiety symptoms (p < 0.001 and p = 0.002, respectively). Compared with SMS, FMS were more likely to have poor sleep quality (p = 0.020). Besides, nurses got significantly higher percentage of poor sleep quality (OR = 1.352, p = 0.016) and insomnia (OR = 1.243, p = 0.041) than doctors. Whereas, the proportion of anxiety symptoms was increased in females than in males (OR = 2.772, p = 0.008). Conclusions: Psychological and sleep disturbances are common among medical staff at work during the COVID-19 pandemic. More psychological intervention should be administrated for FMS, especially for nurses.


Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Feminino , Masculino , Humanos , Pandemias , COVID-19/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , China/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Corpo Clínico , Qualidade do Sono
20.
J Mol Neurosci ; 71(12): 2433-2440, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34160751

RESUMO

Spinal cord injury is a serious disease of the central nervous system, but there is no effective treatment. And zinc is an essential nutrient for human body and participates in many physiological processes, such as immune response, homeostasis, oxidative stress, cell cycle progression, DNA replication, DNA damage repair, apoptosis, and aging. This article mainly summarizes that zinc could predict the prognosis and treat the spinal cord injury. Especially, zinc could help to inhibit inflammation, regulate autophagy, and reduce oxidative stress. However, excessive zinc will damage neurons.


Assuntos
Traumatismos da Medula Espinal/metabolismo , Zinco/metabolismo , Animais , Autofagia , Humanos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Zinco/farmacologia , Zinco/toxicidade
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